FDA approves a key combination therapy for type 2 diabetes mellitus, a device to help patients battle obesity, and another indication for Lucentis.
On February 2, 2015, the FDA approved Glyxambi, an oral therapy combining empagliflozin and linagliptin, giving patients with type 2 diabetes mellitus (T2DM) a new option that combines the actions of both sodium glucose co-transporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors.
Glyxambi combines 10 mg or 25 mg of empagliflozin, an SGLT2 inhibitor, and 5 mg of linagliptin, a DPP-4 inhibitor. It is a tablet, to be given once a day in the morning, according to an announcement from Eli Lilly and Boehringer Ingelheim Pharmaceuticals Inc, makers of the 2 therapies. The new combination therapy is not for persons with type 1 diabetes mellitus and is intended to be a an add-on to metformin, as part of a treatment plan that includes a healthy diet and exercise.
Persons with T2DM will be able to enjoy the advantages of 2 distinct mechanisms of action while only having to take 1 tablet. SGLT2 inhibitors transport glucose out of the system through the urine by blocking reabsorption through the kidneys. DPP-4 inhibitors increase hormones to encourage the pancreas to produce more insulin, and by stimulating the liver to produce less glucose. While not approved for weight loss, the majority of patients who take these therapies have lost weight.
The FDA based its approval on results from a phase 3 clinical trial which found that adults taking Glyxambi as an add-on to metformin showed statistically signicant reductions in glycated hemoglobin (A1C) at 24 weeks compared with adults taking empagliflozin and linagliptin alone. Starting from a baseline A1C of 8%, adults in the trial achieved a mean A1C of 6.9% and 6.7% with Glyxambi, at the doses of 10 mg/5 mg and 25 mg/5 mg, respectively. This compared with A1Cs of 7.3% and 7.4% for empagliflozin alone at 10 mg and 25 mg, respectively, and 7.3% for linagliptin alone at 5 mg.
Common adverse events (AEs) are urinary tract infections (UTIs), although no patient discontinued use due to UTIs. Other AEs are nasopharyngitis and upper respiratory tract infections. Glyxambi should not be taken by patients with severe renal impairment, end-stage renal disease, or dialysis.
FIRST-OF-ITS-KIND OBESITY DEVICE TARGETS NERVE PATHWAY
The FDA on January 14, 2015, approved a new type of weight loss device, one that seeks to take aim at the nerve pathway between the brain and the stomach that controls feelings of hunger and fullness.
Created by EnteroMedics, the Maestro Rechargeable System is the rst device for treatment of obesity to gain approval since 2007. It is intended for use by patients 18 years and older who have been unable to lose weight through traditional programs. Patients must also have a body mass index (BMI) of 35 to 45 and at least 1 other obesity-related comorbidity, such as type 2 diabetes mellitus (T2DM).
BMI, a measurement of body fat based on an individual’s weight and height, is the most frequently used evaluation of whether a patient’s weight is normal, overweight, or obese, but it is sometimes criticized as not the best measure in all circumstances. However, by this measure, more than one-third of adults in the United States are now obese, a fact that has caused alarm among public health ofcials, as it has been linked to rising rates of T2DM and other ailments, including certain types of cancer. The rise in obesity was cited by the FDA in granting the approval.
The Maestro Rechargeable System was approved even though the specific mechanism of how it blocks nerve activity is not fully understood. It features a rechargeable electrical pulse generator, wire leads, and electrodes implanted surgically into the abdomen. It sends intermittent electrical pulses to the trunks in the abdominal vagus nerve, which is involved in regulating the emptying of the stomach and in signaling to the brain that the stomach feels empty or full. External controllers enable the patient to charge the device and healthcare professionals to adjust its settings in order to provide optimal therapy with minimal side effects.
The device was evaluated in a clinical trial with 233 patients with a BMI of 35 or greater. Weight loss and adverse events in 157 patients who received the active Maestro device (the experimental group) were compared with 76 patients in the control group who received a Maestro electrical pulse generator that was not activated. The study found that after 12 months, the experimental group lost 8.5% more of its excess weight than the control group. About half (52.5%) of the patients in the experimental group lost at least 20% of their excess weight, and 38.3% of patients in the experimental group lost at least 25% of their excess weight.
The study did not reach its primary end point, which was that the experimental group lost 10% more excess weight than the control group, but the FDA considered the clinical study and recommendations of an advisory panel as well as a survey of patients who said they would accept the risks of the device. The approval requires a 5-year follow-up study of at least 100 patients.
Serious adverse events included nausea, pain at the neuroregulator site, and vomiting, as well as surgical complications. Other adverse events included pain, heartburn, problems swallowing, belching, mild nausea, and chest pain.
RANIBIZUMAB APPROVED TO TREAT DIABETIC RETINOPATHY IN PATIENTS WITH DME
On February 6, 2015, the FDA expanded the approved indications of ranibizumab to include treatment for diabetic retinopathy (DR) in patients with diabetic macular edema (DME). The drug, administered by a physician as a 0.3-mg injection once a month, is marketed as Lucentis by Genentech.
Diabetic retinopathy is the most common diabetic eye disease and is a leading cause of blindness in adults in the United States. According to the CDC, both type 1 and type 2 diabetes mellitus affect more than 29 million people in the United States; the disease is the leading cause of new blindness among persons aged 20 to 74 years. Diabetic retinopathy becomes more common as persons with the disease age.
“Diabetes is a serious public health crisis, affecting more patients every year,” said Edward Cox, MD, MPH, director of the Ofce of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “(This) approval gives patients with diabetic retinopathy and diabetic macular edema the rst signicant therapy to treat this vision-impairing complication.”
FDA’s approval for the ranibizumab indication came after 2 clinical studies involving 759 participants who were followed for 3 years. In the studies, participants being treated with the therapy showed signicant improvement in the severity of their DR at 2 years compared with patients who did not receive an injection. The most common side effects include bleeding of the conjunctiva, the tissue that lines the inside of the eyelids and covers the white part of the eye; eye pain; oaters; and increased pressure inside the eye (intraocular pressure). Serious side effects include infection within the eyeball (endophthalmitis) and retinal detachments.
The FDA granted ranibizumab for DR with DME breakthrough therapy designation; this occurs at the request of the sponsor if preliminary clinical evidence indicates the drug may demonstrate a substantial improvement over available therapies for patients with serious or life-threatening conditions. The FDA also reviewed the new use under the agency’s priority review program, which provides for an expedited review of drugs that demonstrate the potential to be a signicant improvement in safety or effectiveness in the treatment of a serious condition. Ranibizumab had been approved previously to treat DME and macular edema secondary to retinal vein occlusions.
FDA approves first-in-class Glyxambi empagliflozin/linagliptin tablets for adults with type 2 diabetes [press release]. Ridgefield, CT, and Indianpolis, IN: PRNewswire; February 2, 2015.
FDA approves first-of-kind device to treat obesity [press release]. Silver Spring, MD: FDA Newsroom; January 14, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
FDA approves Lucentis to treat diabetic retinopathy in patients with diabetic macular edema [press release]. Silver Spring, MD: FDA Newsroom; February 6, 2015. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm433392.htm.